Hello all,
I have a questions regarding calculation of volume of distribution and clearance for single dose of Amphotericin B injection. Study design is open label, randomized, two-treatment, two period, two-sequence, single dose, crossover, comparative pharmacokinetic study in healthy adult human subjects under fed conditions.
Study was carried out with following objective
To compare the rate and extent of absorption of amphotericin B after intravenous
administration of single dose of Amphotericin B liposome for injection (each vial
containing amphotericin 50 mg encapsulated in liposomes) with that of AmBisome® liposome for injection (each vial containing amphotericin 50 mg encapsulated in liposomes) in healthy adult human subjects in a randomized crossover study under fed conditions. The plasma pharmacokinetics of free and liposomal amphotericin were evaluated.
Dose mode of administration is single dose of Amphotericin B liposome for injection (3 mg/kg body weight). Dose was given to subjects with respective subject weight
i.e. suppose subject No.01, weight 73 and dose 3mg/kg then total dose= 73 kg * 3 mg/kg =219 mg.
I had calculated administration VD and CL based on the non-compartmental model using IV infusion dose type. Following information’s was provided in dosing sheet in winNonlin software.
sub-1, period-1, dose-219mg, time of dose-0,
Length of Infusion-2
sub-1, period-2, dose-219mg, time of dose-0,
Length of Infusion-2.01
Plasma Concentration data is as below
Sub Seq Per Form Time (hr) Conc (μg/mL)
1 B 1 T 0 0
1 B 1 T 0.5 0
1 B 1 T 1 2.19
1 B 1 T 1.33 4.86
1 B 1 T 1.67 6.21
1 B 1 T 2 8.24
1 B 1 T 2.33 7.6
1 B 1 T 2.67 6.77
1 B 1 T 3 6.49
1 B 1 T 3.5 6.85
1 B 1 T 4 7.99
1 B 1 T 5 7.22
1 B 1 T 6 8.2
1 B 1 T 8 7.7
1 B 1 T 10 8.98
1 B 1 T 12 8.08
1 B 1 T 16 6.58
1 B 1 T 24 3.56
1 B 1 T 36 Missing
1 B 1 T 48 1.31
1 B 1 T 72 0.61
1 B 1 T 96 0.35
1 B 1 T 120 0.25
1 B 1 T 144 0.23
1 B 1 T 168 Missing
1 B 2 R 0 0
1 B 2 R 0.5 0
1 B 2 R 1 1.58
1 B 2 R 1.33 2.81
1 B 2 R 1.67 4.24
1 B 2 R 2 5.66
1 B 2 R 2.33 5.69
1 B 2 R 2.67 6.11
1 B 2 R 3 5.24
1 B 2 R 3.5 5.85
1 B 2 R 4 5.89
1 B 2 R 5 7.38
1 B 2 R 6 6.31
1 B 2 R 8 5.67
1 B 2 R 10 4.62
1 B 2 R 12 4.89
1 B 2 R 16 4.45
1 B 2 R 24 2.56
1 B 2 R 36 2.11
1 B 2 R 48 0.78
1 B 2 R 72 0.57
1 B 2 R 96 0.39
1 B 2 R 120 0.27
1 B 2 R 144 0.25
1 B 2 R 168 0
PK parameter calculations VD and CL values obtained from winNonlin were not matching with reference article
WinNonlin results of VD and CL is as below
Sub VD (mL) CL (mL/hr)
1 29759.19 833.3955
1 82120.74 1029.759
sub-1, period-1, VD (mL)-29759.19, CL (mL/hr)-833.3955
sub-1, period-2, VD (mL)-82120.74, CL (mL/hr)-1029.759
Could anyone please guide me how to estimate VD and CL in mL/kg and mL/hr/kg in winNonlin software.
In the NCA-setup by selecting option Normalization and kg. I get Vd in mL/Kg and clearance in mL/h/kg but till value were not matches with SPC report.
when I selecting option Normalization and g, I get same value as that of Normalization and kg.
Reference: Prescribing information of AmBisome® (amphotericin liposome for injection from Astellas Pharma US, Inc. [cited 18 December, 2013]. www.accessdata.fda.gov/drugsatfda_docs/l...12/050740s021lbl.pdf
Thanks in advance
Regards
Amol
Edited by Simon Davis, 28 October 2014 - 05:51 AM.
restore formatting lost after migration